Usual Adult Dose for Breast Cancer

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Adult Dose for Kaposi's Sarcoma

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Adult Dose for Testicular Cancer

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Adult Dose for Hodgkin's Disease

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Adult Dose for Mycosis Fungoides

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Adult Dose for Choriocarcinoma

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Adult Dose for Lymphoma

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Adult Dose for Histiocytosis

Because of the variation in the depth of the leukopenic response following therapy, the manufacturer recommends that the dose not be given more frequently than once every 7 days. The manufacturer outlines the following conservative incremental approach to dosage every 7 days for adults:

• First dose: 3.7 mg/m2 IV
• Second dose: 5.5 mg/m2 IV
• Third dose: 7.4 mg/m2 IV
• Fourth dose: 9.25 mg/m2 IV
• Fifth dose: 11.1 mg/m2 IV
• This progression may be followed up to a maximum dosage of 18.5 mg/m2 IV. The dose should not be increased after that dose which reduces the white cell count to approximately 3000 cells/mm3. In some adults, 3.7 mg/m2 IV may produce this leukopenia; other adults may require more than 11.1 mg/m2 IV; and, very rarely, as much as 18.5 mg/m2 IV may be necessary. For most adult patients, the weekly dose will be 5.5 to 7.4 mg/m2 IV.
• When the dose which produces the above degree of leukopenia has been established, a dose of one increment smaller than this should be administered at weekly intervals for maintenance so the patient is receiving the maximum dose that does not cause leukopenia. Even though 7 days have elapsed, the next dose should not be given until the white cell count has returned to at least 4000/mm3. In some cases, oncolytic activity may be encountered before leukopenic effect. When this occurs, there is no need to increase the size of subsequent doses.

Uses:
Frequently Responsive Malignancies:

• Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye staging system)
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated)
• Histiocytic lymphoma
• Mycosis fungoides (advanced stages)
• Advanced carcinoma of the testis
• Kaposi's sarcoma
• Letterer-Siwe disease (histiocytosis X)

Less Frequently Responsive Malignancies:

• Choriocarcinoma resistant to other chemotherapeutic agents
• Carcinoma of the breast unresponsive to appropriate endocrine surgery and hormonal therapy

Usual Pediatric Dose for Testicular Cancer

Initial doses of this drug in pediatric patients varies depending on the schedule used and whether it is administered as a single agent or incorporated within a chemotherapeutic regimen:

• As a single agent for Letterer-Siwe disease (histiocytosis X), the initial dose is 6.5 mg/m2 IV
• When used in combination with other chemotherapeutic agents for Hodgkin's disease, the initial dose is 6 mg/m2 IV
• For testicular germ cell carcinomas, the initial dose is 3 mg/m2 IV in a combination regimen
• Dose modifications should be guided by hematologic tolerance.

Usual Pediatric Dose for Hodgkin's Disease

Initial doses of this drug in pediatric patients varies depending on the schedule used and whether it is administered as a single agent or incorporated within a chemotherapeutic regimen:

• As a single agent for Letterer-Siwe disease (histiocytosis X), the initial dose is 6.5 mg/m2 IV
• When used in combination with other chemotherapeutic agents for Hodgkin's disease, the initial dose is 6 mg/m2 IV
• For testicular germ cell carcinomas, the initial dose is 3 mg/m2 IV in a combination regimen
• Dose modifications should be guided by hematologic tolerance.

Usual Pediatric Dose for Histiocytosis

Initial doses of this drug in pediatric patients varies depending on the schedule used and whether it is administered as a single agent or incorporated within a chemotherapeutic regimen:

• As a single agent for Letterer-Siwe disease (histiocytosis X), the initial dose is 6.5 mg/m2 IV
• When used in combination with other chemotherapeutic agents for Hodgkin's disease, the initial dose is 6 mg/m2 IV
• For testicular germ cell carcinomas, the initial dose is 3 mg/m2 IV in a combination regimen
• Dose modifications should be guided by hematologic tolerance.

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

The manufacturer recommends a 50% dose reduction for patients having a direct serum bilirubin value above 3 mg/100 mL.

Precautions

US BOXED WARNINGS:
FOR INTRAVENOUS USE ONLY-FATAL IF GIVEN BY OTHER ROUTES.

• Caution: This preparation should be administered by individuals experienced in the administration of vinblastine. It is extremely important that the IV needle or catheter be properly positioned before any of the drug is injected. Leakage into surrounding tissue during IV administration may cause considerable irritation. If extravasation occurs, the injection should be discontinued immediately, and any remaining portion of the dose should then be introduced into another vein. Local injection of hyaluronidase and the application of moderate heat to the area of leakage help disperse the drug and are thought to minimize discomfort and the possibility of cellulitis.
• The intrathecal administration of vinblastine usually results in death.
• Syringes containing this product should be labeled, using the auxiliary sticker provided, to state ''FOR INTRAVENOUS USE ONLY-FATAL IF GIVEN BY OTHER ROUTES.''
• Extemporaneously prepared syringes containing this product must be packaged in an overwrap which is labeled ''DO NOT REMOVE COVERING UNTIL MOMENT OF INJECTION. FOR INTRAVENOUS USE ONLY-FATAL IF GIVEN BY OTHER ROUTES.''
• After inadvertent intrathecal administration of vinca alkaloids, immediate neurosurgical intervention is required to prevent ascending paralysis leading to death. In a very small number of patients, life-threatening paralysis and subsequent death was averted but resulted in devastating neurological sequelae, with limited recovery afterwards.
• There are no published cases of survival following intrathecal administration of vinblastine to base treatment on. However, based on the published management of survival cases involving vincristine, if vinblastine is mistakenly given by the intrathecal route, the following treatment should be initiated immediately after the injection:

1) Removal of as much CSF as is safely possible through the lumbar access.
2) Insertion of an epidural catheter into the subarachnoid space via the intervertebral space above initial lumbar access and CSF irrigation with lactated Ringer's solution. Fresh frozen plasma should be requested and, when available, 25 mL should be added to every 1 L of lactated Ringer's solution.
3) Insertion of an intraventricular drain or catheter by a neurosurgeon and continuation of CSF irrigation with fluid removal through the lumbar access connected to a closed drainage system. Lactated Ringer's solution should be given by continuous infusion at 150 mL/hr, or at a rate of 75 mL/hr when fresh frozen plasma has been added as above.

• The rate of infusion should be adjusted to maintain a spinal fluid protein level of 150 mg/dL.
• The following measures have also been used in addition but may not be essential: Glutamic acid, 10 g IV over 24 hours, followed by 500 mg 3 times daily by mouth for 1 month. Folinic acid IV as a 100 mg bolus and then infused at a rate of 25 mg/hr for 24 hours, then bolus doses of 25 mg every 6 hours for 1 week. Pyridoxine 50 mg IV over 30 minutes every 8 hours. Their roles in the reduction of neurotoxicity are unclear.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Patient advice:

• Advise patients to promptly report any signs of leucopenia, such as sore throat, fever, chills or stomatitis, and to avoid constipation.
• Advise patients that treatment-related alopecia is likely but is in most cases reversible.